This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Theoretical studies of biological systems allow for information on atomic-level contributions to structure-function relationships, including high-energy states difficult to study experimentally, to be obtained. Such knowledge can lead to a better understanding of a variety of physiological processes, including those associated with disease states, ultimately leading to the development of treatments for such disease states. The general objectives of the present proposal are 1) to extend the applicability and accuracy of empirical force field based theoretical studies of biological macromolecules 2) apply theoretical methods to relate atomic details of the structural and dynamic properties of biomolecules to their biological activity and 3) apply computational methods for the identification of compounds with the potential to act as inhibitors for proteins of therapeutic interest.